Glycan
attached to asparagine.]] A glycan is a chain of sugar molecules, also known as a polysaccharide. Glycans can become attached to proteins before folding is complete, and are important in determining how the protein folds. In Foldit, glycans are a rare feature, seen in only three puzzles to date. In Puzzle 879: Ebola Binder Design with Disulfides and Puzzle 884b: 74 Residue Ebola Binder Design, segment 134 had a glycan attached. Puzzle 1378b: Hemagglutinin Binder Design: Loop Graft had a glycan attached to segment 30. In these three puzzles, the glycan was attached to an asparagine. The glycan itself appears to be the same in each puzzle. This is a common form of N-linked glycosylation, where the "N" refers to nitrogen. The nitrogen here is at the end of the asparagine sidechain. (Conveniently, the code for asparagine is also "N" or "n".) attached to asparagine. The glycan seems to be the same as the one seen in puzzles 879 and 884b.]] The same glycan appears in 879, 884b, and 1378b. The exact chemical name for this glycan is not known. The wikipedia article Glycan mentions several possible N-linked glycans, such as galactose, neuraminic acid, and mannose. In all three puzzles, the segment with the glycan had an atom count of 89, as opposed to the normal (mid-chain) atom count of 14 for asparagine. Both the backbone and sidechain of the glycosylated segment were locked, so the glcyan segment had only one rotamer in all three puzzles. For an N-linked glycan, the nearby sequence, known as the sequon is important. In general, it must start with asparagine, followed by any amino acid except proline, and then either serine or threonine. (Rarely, cysteine or other amino acids may appear instead of serine or threonine.) In puzzles 879 and 884b, the sequon was asparagine-glutamate-threonine ("net"). In puzzle 1378b, the sequence was asparagine-alanine-threonine ("nat"). Foldit identifies a glycosylated segment as "unknown", and returns "unk" for the amino acid code. Recipes such as AA Edit and print protein use the code "x" in place of "unk". The code "x" means "any amino acid", and sequences containing "x" can be used to search the PDB and similar sources. Similar proteins found in PDB will probably have "n" for asparagine found in place of the "x". Although the glycan is no longer a standard amino acid, it's still part of an amino acid chain. In Foldit, the segment with the glycan should have a secondary structure of helix, sheet, or loop, with codes H, E, or L. In contrast, a true ligand is not part of an amino acid chain, and has a secondary structure code of "M" for molecule. In addition to the N-linked glycans seen in 879, 884b, and 1378b, there are also O-linked glycans, which can be attached to the oxygen atoms in the sidechains of serine or threonine. No O-linked glycans are known to have appeared in Foldit puzzles. A Foldit developer chat on 18 July 2017 discussed glycans in relation to puzzle 1378b, although the puzzle was consistently misidentified as "1387b". A blog post contained the questions for the chat. Category:Glossary Category:Biochemistry